Chronic vs Acut

Question 1

Beneficial and Detrimental Effects of Neuroinflammation

Answer 1

Neuroinflammation is a double-edged sword: it plays a protective role but can also contribute to disease progression if unregulated.

Beneficial Effects:
✅ Protection Against Infections & Injury

Microglia and astrocytes detect infections and release pro-inflammatory cytokines to fight pathogens.
Helps clear damaged cells and repair tissues after injury (e.g., traumatic brain injury).
✅ Phagocytosis of Toxic Aggregates

Microglia engulf and degrade toxic proteins, like beta-amyloid in Alzheimer’s disease.
✅ Synaptic Remodeling

Microglia help in pruning excess synapses, crucial for normal brain function.
Detrimental Effects:
❌ Chronic Inflammation & Neurotoxicity

Excessive inflammation leads to neuronal damage and cell death.
Pro-inflammatory cytokines (e.g., TNF-α, IL-1β) can disrupt synapses, leading to cognitive decline.
❌ Blood-Brain Barrier (BBB) Breakdown

Chronic inflammation damages the BBB, allowing toxins and immune cells into the brain, worsening conditions like Multiple Sclerosis (MS).
❌ Contributes to Neurodegenerative Diseases

In Alzheimer’s, Parkinson’s, and Multiple Sclerosis, chronic inflammation accelerates neuronal loss.
📌 Key Takeaway: Neuroinflammation is essential for defense and repair, but chronic inflammation worsens neurodegenerative diseases.

Question 2

Neuroinflammation After Bacterial/Viral Infections

Answer 2

Brain infections trigger neuroinflammatory responses that can either help clear pathogens or cause long-term damage.

Common Infections Causing Neuroinflammation:
Bacterial Infections → Meningitis, Tuberculosis
Viral Infections → Herpes Simplex Encephalitis, HIV, COVID-19
Neuropathology of Infections:
Meningitis: Inflammation of the leptomeninges caused by bacterial or viral infections.
Encephalitis: Inflammation of brain parenchyma (e.g., Herpes Simplex Encephalitis).
Meningoencephalitis: A combination of both.
Herpes Simplex Encephalitis (HSE) as an Example
Affects the temporal lobe → causes memory loss, seizures, and personality changes.
Leads to hemorrhagic necrosis (brain tissue destruction).
Microglial nodules and perivascular lymphocyte infiltration are key markers of inflammation.
COVID-19 and Neuroinflammation
Does not cause direct encephalitis in most cases.
Some destructive perivascular lesions and axonal injury found in rare cases.
Hypoxia-induced amyloid plaque formation observed in some COVID-19 patients, raising concerns about its link to neurodegeneration.
📌 Key Takeaway: Neuroinflammation following infections can lead to brain damage and chronic neurological disorders if not resolved.

Question 3

Neuroinflammation in Alzheimer’s Disease (AD)

Answer 3

Alzheimer’s is a progressive neurodegenerative disease, and chronic neuroinflammation is a key factor in its pathology.

Neuropathology of AD:
🔸 Amyloid Plaques → Misfolded beta-amyloid proteins accumulate in the brain.
🔸 Neurofibrillary Tangles → Tau protein aggregates inside neurons.
🔸 Brain Shrinkage → Atrophy of hippocampus and cortex.

Role of Neuroinflammation in AD:
Microglia surround plaques but fail to clear them, releasing pro-inflammatory cytokines instead.
Microglia excessively prune synapses, contributing to memory loss.
Astrocytes release cytokines, causing further neuronal damage.
Blood-brain barrier remains largely intact, but chronic inflammation accelerates neurodegeneration.
📌 Key Takeaway: Neuroinflammation worsens Alzheimer’s disease by promoting synapse loss and neuronal death.

Question 4

Disease-Specific Neuroinflammation

Answer 4

Acute Infections (e.g., Encephalitis, Meningitis)
==> Severe inflammation, BBB breakdown, rapid onset

Multiple Sclerosis (MS) ==> Chronic inflammation, BBB moderately intact, immune cells attack myelin

Alzheimer’s Disease ==> Chronic inflammation, BBB largely intact, slow neurodegeneration

Question 5

stages of alzheimers

Answer 5

1️⃣ Preclinical Stage (No Symptoms)

Amyloid plaques start forming in the brain.
No significant memory loss yet.
2️⃣ Mild Cognitive Impairment (MCI)

Tau tangles start forming, leading to subtle memory problems.
3️⃣ Early Alzheimer’s

Hippocampal atrophy begins.
Forgetfulness, difficulty finding words.
4️⃣ Moderate Alzheimer’s

Amyloid plaques and tangles spread.
More severe memory loss, confusion, mood changes.
5️⃣ Severe Alzheimer’s

Widespread brain atrophy.
Loss of ability to speak, recognize family, perform daily tasks.

Question 6

Key Neuropathological Features of Alzheimer’s Disease

Answer 6

Amyloid Plaques (Extracellular)
🔹 Cause: Misfolded beta-amyloid (Aβ) proteins accumulate outside neurons.
🔹 Effect: Disrupts cell communication, triggers inflammation, and leads to neuronal death.
🔹 Location: Found in the hippocampus and cortex, regions important for memory and cognition.

~~~

Neurofibrillary Tangles (Intracellular)
🔹 Cause: Hyperphosphorylation of tau protein leads to twisted neurofibrillary tangles inside neurons.
🔹 Effect: Disrupts microtubule transport, leading to cell death.
🔹 Location: Starts in the entorhinal cortex and hippocampus and spreads throughout the brain.

Question 7

Is microglial activation a good/bad thing in alzheimers

Answer 7

good : phagocytosis of beta amyloid = clearance of plaques

bad :
- excessive synapse pruning (microglia remove weak or unnecessary synapses to refine neural circuits.)
=> mistakenly prune healthy synapses
- release of proinflammatory cytokines (vicious cycle of inflammation)
- promotes further beta amyloid deposition (Cytokines increase amyloid precursor protein (APP) cleavage, leading to more beta-amyloid plaques.)
- promotes neurofibrillary tangle formation (Pro-inflammatory cytokines activate kinases that phosphorylate tau)